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Biomedical subjects

Yuichi Ueda

Publications and source records attributed to Yuichi Ueda.

53 records · Page 3Linked to original sources

Long-term clinical performance of AAI pacing in patients with sick sinus syndrome: a comparison with dual-chamber pacing.

AIMS: In this clinical study, we compared two groups of age-matched patients, AAI and DDD, to evaluate the clinical benefits of AAI pacing in patients with sick sinus syndrome (SSS) and normal atrioventricular (AV) conduction. METHODS AND RESULTS: Ninety-five patients with SSS implanted with AAI pacemakers were compared with 101 SSS patients implanted with DDD pacemakers. Mortality, chronic atrial fibrillation, lead survival rates, and reoperation rates were compared by Kaplan-Meier analysis. Eight AAI devices were switched to DDD due to high-degree (grade 2-3) AV block. The incidence of high-degree AV block was 1.104%/year, with a freedom rate of 88.6% at 10 years. There were no significant differences between the two groups in survival rates (87.8% in AAI vs. 93.4% in DDD at 10 years), freedom from atrial fibrillation (93.6% vs. 90.6%), or freedom from reoperation (71.3% vs. 76.3%). On the other hand, lead failure was twice as frequent in the DDD group than in the AAI group (relative risk=2.045, P=0.0382). CONCLUSION: AAI pacing, a simple system using a single lead and single-chamber pacemaker, can achieve a clinical outcome similar to that of the DDD mode in patients with SSS and normal AV conduction.

Adolescent↗

STAT3 and MAPK in human lung cancer tissues and suppression of oncogenic growth by JAB and dominant negative STAT3.

To search for the signaling events in lung carcinoma relevant to its tumorigenesis, we investigated the phosphorylation of MAPK and STAT3 in human lung carcinoma tissues and their paired normal tissues. Although relative amounts of MAPK levels differed among the cases examined, no clear difference in MAPK levels was observed between tumor tissues and their paired normal tissues. Of 79 cases examined, only 7 cases (8.9%) showed tumor-specific phosphorylation of MAPK, whereas 41 cases (52%) showed more than 2-fold lower levels of MAPK phosphorylation in tumor tissues. In contrast to MAPK, 42 cases (53%) showed tumor-specific increase in STAT3 expression. In addition, 15 cases (19%) showed tumor-specific increase of STAT3 phosphorylation and 51 cases (65%) had STAT3 phosphorylation proportional to its expression. Moreover, exogenous expression of either JAB or dominant negative STAT3 in lung carcinoma cell lines led to the suppression of STAT3 phosphorylation and the drastic reduction of anchorage- independent growth of the cells. Taken together, our results suggest that JAK-STAT3 signaling has a pivotal role for oncogenic growth of lung carcinoma cells.

Carrier Proteins↗

Long-term outcome after mitral valve replacement with preservation of continuity between the mitral annulus and the papillary muscle in patients with mitral stenosis.

BACKGROUND AND AIM OF THE STUDY: The effect on left ventricular performance of mitral valve replacement (MVR) with preservation of continuity between the mitral annulus and papillary muscle was studied in patients with mitral stenosis (MS). METHODS: Forty patients with MS who underwent MVR between 1986 and 1995 and had long-term echocardiographic follow up were studied retrospectively. Eighteen patients had conventional MVR (CMVR group), and 22 (PMVR group) had either preservation of autologous chordae tendineae (n = 6) or replacement of the chordae with expanded polytetrafluoroethylene sutures (n = 16). RESULTS: Preoperatively, there were no significant differences between the two groups in age, body surface area, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), fractional shortening (FS) or ejection fraction (EF). At 3.1-6.5 years after surgery, periodic echocardiography showed significant differences (p <0.05) in LVESD (35.8 versus 31.6 mm, respectively, in the CMVR and PMVR groups) and FS (31.8% versus 38.1%). At 6.6-9.7 years postoperatively, no significant differences were observed between the two groups in FS, but LVESD was significantly greater in the CMVR group than in the PMVR group (37.3 versus 31.5 mm). CONCLUSION: In the long term, MVR with preservation of continuity between the mitral annulus and papillary muscle improves systolic left ventricular performance in patients with MS.

Aged↗

Loss of heterozygosity of chromosome 12p does not correlate with KRAS mutation in non-small cell lung cancer.

Activating mutations of RAS gene families have been found in a variety of human malignancies, including lung cancer, suggesting their dominant role in tumorigenesis. However, several studies have shown a frequent loss of the wild-type KRAS allele in the tumors of murine models and an inhibition of oncogenic phenotype in tumor cell lines by transfection of wild-type RAS, indicating that wild-type RAS may have oncosuppressive properties. To determine whether loss of wild-type KRAS is involved in the development of human lung cancer, we investigated the mutations of KRAS, NRAS and BRAF in 154 primary non-small cell lung cancers (NSCLCs) as well as 10 NSCLC cell lines that have been shown to have KRAS mutations. We also determined the loss of heterozygosity status of KRAS alleles in these tumors. We detected point mutations of KRAS in 11 (7%) of 154 NSCLCs, with 10 cases at codon 12 and 1 at codon 61, but no mutations of NRAS or BRAF were found. Using the laser capture microdissection technique, we confirmed that 9 of the 11 tumors and 7 of the 10 NSCLC cell lines retained the wild-type KRAS allele. Among the cell lines with heterozygosity of mutant and wild-type KRAS, all of the cell lines tested for expression were shown to express more mutated KRAS than wild-type mRNA, with higher amounts of KRAS protein also being expressed compared to the cell lines with a loss of wild-type KRAS allele. In addition, among 148 specimens available for immunohistochemical analysis, 113 (76%) showed positive staining of KRAS, indicating that the vast majority of NSCLCs continue to express wild-type KRAS. Our findings indicate that the wild-type KRAS allele is occasionally lost in human lung cancer, and that the oncogenic activation of mutant KRAS is more frequently associated with an overexpression of the mutant allele than with a loss of the wild-type allele in human NSCLC development.

Base Sequence↗

Beta-catenin inhibits cell growth of a malignant mesothelioma cell line, NCI-H28, with a 3p21.3 homozygous deletion.

We have found that a malignant mesothelioma cell line, NCI-H28, had a chromosome 3p21.3 homozygous deletion containing the beta-catenin gene (CTNNB1), which suggested that the deletion of beta-catenin might have a growth advantage in the development of this tumor. To determine whether beta-catenin has a growth-inhibitory activity, we transfected wild-type beta-catenin, Ser37Cys mutant beta-catenin as an activated type, and C-terminus deletion mutant beta-catenin that lacks the transcription activity, into the NCI-H28 cells. A non-small cell lung cancer cell line, NCI-H1299, which expressed endogenous beta-catenin, was also studied. We tested the localization of exogenous beta-catenin in the NCI-H28 cells with immunofluorescence, and found that the wild-type beta-catenin and the C-terminus deletion mutant were more strongly expressed in the plasma membrane and cytoplasm than in the nucleus, while the Ser37Cys mutant was more in the nucleus than in the cytoplasm. By using luciferase-reporter assay, the beta-catenin/T-cell factor 4-mediated transactivity of the Ser37Cys mutant was shown to be higher than that of the wild-type beta-catenin in both cell lines. However, the transactivity of the C-terminus deletion mutant was strongly reduced in both. Colony formation of the NCI-H28 cells was reduced by 50% after transfection with the wild-type beta-catenin, and 60% with the Ser37Cys mutant, but only 20% with the C-terminus deletion mutant compared to the vector control. Inhibition of colony formation in NCI-H28 cells was because of apoptosis, manifested by positive staining of Annexin V and TUNEL assays in transfected cells. In contrast, when transfected with the wild-type beta-catenin, no significant reduction in colony formation was seen in beta-catenin wild-type NCI-H1299 cells. In conclusion, our data indicate that inactivation of beta-catenin by a 3p21.3 homozygous deletion might be a crucial event in the development of the mesothelioma NCI-H28 cells. Thus, while beta-catenin is well known to be a positive growth-stimulating factor for many human cancers, it can also act as a potential growth suppressor in some types of human cancer cells.

Annexin A5↗

Overexpression of calpastatin by gene transfer prevents troponin I degradation and ameliorates contractile dysfunction in rat hearts subjected to ischemia/reperfusion.

Calpain is a Ca(2+)-activated neutral protease that supposedly plays a key role in myocardial dysfunction following ischemia/reperfusion, by degrading certain proteins involved in the contraction mechanism. It is possible that overexpression of calpastatin, an endogenous calpain inhibitor, lessens contractile dysfunction in the heart after reperfusion by preventing cardiac troponin I (TnI) degradation. This claim is tested by overexpression of human calpastatin (hCS) in rat hearts ex vivo using an adenovirus vector; the hearts were transplanted heterotopically into the abdomens of recipient rats to allow expression of hCS. On the fourth day after surgery, the hearts were excised and perfused in vitro to study their recovery from 30 min of global ischemia, which was followed by 60 min of reperfusion. The peak recovery of the left ventricular developed pressure (LVDP), and the values of its first derivative (max dP/dt, min dP/dt) in the hCS-overexpressed hearts were 88.9 +/- 4.8%, 90.8 +/- 9.2% and 106.4 +/- 9.8%, respectively; these values were all significantly greater than in the control hearts transfected with LacZ alone (51.4 +/- 6.9%, 52.6 +/- 8.1% and 54.7 +/- 6.6%, P < 0.05). In western blot analysis of ventricular myocardial samples (at 60-min reperfusion) using a monoclonal anti-TnI antibody, two bands corresponding to intact TnI (30 kDa) and TnI fragments (27 kDa) were distinguished. The fraction of 27-kDa TnI (percent of total TnI immunoreactivity) in hCS-overexpressed hearts was significantly less than the controls (5.7 +/- 2.7% vs. 18.1 +/- 3.2%, P < 0.05), implying a protective action of hCS against TnI degradation. These results suggest that adenovirus-mediated overexpression of hCS in the heart could be a novel biological means to minimize myocardial stunning by ischemia/reperfusion.

Adenoviridae↗

Functional recovery of the native heart after cardiomyoplasty in sheep with heart failure: passive and dynamic effects of volume loading.

BACKGROUND: Dynamic cardiomyoplasty (d-CMP) encourages reverse remodeling and improved contractility and stroke work (SW) efficiency of the failing native heart. This contrasts with passive cardiomyoplasty (p-CMP), which provides "passive girdling." To further evaluate pump recovery we assessed native left ventricular performance (without assist) 6 months after dynamic and passive CMP in sheep with heart failure with acute volume loading. METHODS: Heart failure (left ventricular ejection fraction 26%+/-8%) induced by coronary microembolization was followed by CMP in 11 sheep. After 8 weeks of muscle "training," paced cardiac assist was undertaken in the d-CMP group (n = 6). Five sheep with heart failure served as controls. Six months later the pressure-volume relationship was derived before and after volume loading by colloid solution. Latissimus dorsi muscle pacing was previously ceased in the d-CMP group. RESULTS: Volume loading increased left ventricular end-diastolic volume and pressure in all groups. After volume loading in d-CMP, the SW and pressure-volume area were increased, and SW efficiency remained unchanged. In p-CMP neither variable changed, whereas in control heart failure SW efficiency decreased due to a rise in pressure-volume area with stable SW. CONCLUSIONS: Based on response to volume loading, the failing native heart after 6 months of d-CMP showed functional recovery from "active girdling," whereas p-CMP prevented functional deterioration through passive girdling. The failing control heart progressively deteriorated.

Animals↗

Repetitive atrial flutter as a complication of the left-sided simple maze procedure.

BACKGROUND: Of 41 patients who had undergone a left-sided simple maze procedure, 4 (9.8%) developed repetitive tachycardia due to atrial flutter, and required radiofrequency catheter ablation. Linear ablation of the right atrial isthmus was effective to treat atrial flutter. METHODS: We conducted an electrophysiologic study of atrial flutter and determined its reentry circuit on the atrium. We consider how to reduce atrial flutter after the left-sided simple maze procedure. RESULTS: Common atrial flutter through the right atrial isthmus was induced in all 4 patients, and linear ablation on the right atrial isthmus was effective in 3 of these. An incisional atrial flutter around the right atriotomy was also induced in 2 of 4 patients; both were successfully treated by linear ablation between the right atriotomy and the inferior vena cava. CONCLUSIONS: Common atrial flutter through the right atrial isthmus is a risk after the left-sided simple maze procedure. When a left-sided simple maze procedure is performed, sufficient cryoablation on the right atrial isthmus of the arrested heart should be administered to prevent postoperative atrial flutter.

Adult↗

Cerebrospinal dysfunction after endovascular stent-grafting via a median sternotomy: the frozen elephant trunk procedure.

BACKGROUND: Endovascular stent grafting through a median sternotomy for a distal arch aneurysm (the frozen elephant trunk procedure) is an alternative to synthetic graft replacement. But spinal cord dysfunction can easily occur as a complication after surgery. Although its cause is uncertain, some attempts at prevention have been instituted. We address the mechanism of spinal cord dysfunction and evaluate the efficacy of our preventive measures. METHODS: There were 22 men and 2 women with an average age of 71 (59 to 83) years. There were 22 true aneurysms (13 fusiform, nine saccular), one chronic dissection, and one penetrating aortic ulcer. The following strategies for prevention of spinal cord dysfunction were utilized: low flow perfusion through both axillary arteries (n = 10); pigtail catheter guidance (n = 19); use of a shorter graft with anchoring sutures (n = 12); flooding of the operative field with carbon dioxide (n = 7); aortic unclamping (n = 7), and use of ultra-thin woven Dacron grafts (n = 15). RESULTS: There was no operative mortality, but cerebrospinal dysfunction complicated four cases (17%): one paraplegia, one stroke along the basilar artery, and two cases of temporary spinal cord dysfunction (paresthesia of the right leg and urinary disturbance). Cerebrospinal dysfunction tended to occur in fusiform aneurysms (31%, p = 0.044). Except when low flow antegrade perfusion through both the axillary arteries was utilized, which resulted in no cases of paraplegia or paraparesis (p = 0.064), the methods used for prevention of cerebrospinal dysfunction appeared to have little efficacy. CONCLUSIONS: Cerebrospinal dysfunction is a serious complication of the frozen elephant trunk procedure. Its cause has not been clarified, but it tends to occur in fusiform-type aneurysms. Antegrade perfusion through both axillary arteries while the aorta is open may be helpful in its prevention.

Aged↗

Endovascular treatment for intracranial mycotic aneurysms prior to cardiac surgery.

The management of patients with infective endocarditis complicated by intracranial mycotic aneurysms is controversial. We present the case of a 21-year-old man who suffered from mitral regurgitation with small vegetations due to infective endocarditis. The problem was associated with a ruptured aneurysm on the right anterior cerebral artery and an unruptured aneurysm on the left middle cerebral artery. Endovascular embolization of these aneurysms and subsequent mitral valve repair led to a successful outcome.

Adult↗

The value of caval division in the maze procedure with valve surgery.

Operative predictors for successful elimination of atrial fibrillation (AF) following the maze procedure are not yet known. We have often divided the superior vena cava (SVC) during the maze procedure, not to eliminate AF but in order to explore the mitral valve. However, in multivariate analysis of 79 patients, the division of SVC, as well as the duration of AF, was found to be the strongest predictor of AF elimination. The explanation of this observation is not clear, but denervation of the cardiac autonomic nervous system or the existence of paroxysmal AF originating from the SVC could be involved.

Atrial Fibrillation↗

Optimal size of prostheses for functioning of the aortic prosthetic valve in aortic and mitral valve replacement with annular enlargement through Manouguian's technique.

There is not yet agreement about the optimal size of the prostheses in aortic and mitral valve replacement with Manouguian's technique. In this technique, the aortic prosthetic valve can be pushed upon the mitral prosthesis which may cause dysfunction of the aortic prosthetic valve. The aim of this study was to clarify the size of the prostheses needed to avoid dysfunction of the aortic prosthetic valve. Three patients underwent aortic and mitral valve replacement through this procedure. Two of them had active aortic and mitral valve endocarditis. Aortomitral continuity involved with abscesses could be approached and completely excised using this technique. All patients survived the operation, but 1 of them suffered aortic mechanical valve dysfunction for the reason stated. Anatomical analysis of the geometrical relation of the 2 prosthetic valves suggests that the mitral annulus should be enlarged less than 25 mm to avoid dysfunction of the aortic prosthetic valve.

Adult↗

Mid-term results of an endovascular stent-graft by means of median sternotomy for distal aortic arch aneurysm.

Migration and perigraft leakage are major problems after endovascular stent graft (EVG) by means of median sternotomy for distal aortic arch aneurysm. Anchoring sutures have been applied to prevent these problems. We evaluate the mid-term results and the efficacy of anchoring sutures. The operation was performed on 19 men and 2 women with a mean age of 70 years (range, 59-81). The aneurysms were 19 true (12 fusiform, 7 saccular), 1 chronic dissection, and 1 penetrating aortic ulcer. EGVs were implanted by way of the aortic arch under retrograde cerebral perfusion in 13 patients and selective cerebral perfusion in 8. Total arch replacement was performed in 2 patients, and aortocoronary bypass grafting in 4. Anchoring sutures to fix the EVG were applied in 9 patients. The average follow-up period was 28 months (range, 2-56). There were no operative mortalities, but 1 paraplegia, 1 stroke, and 2 cases of temporary spinal cord dysfunction occurred. All aneurysms were thrombosed completely after surgery and reduced in diameter (66.9 +/- 17.4 mm to 57.3 +/- 15.7 mm, p < 0.0001). EVG-related complications arose in 4 patients. A chronic Type B dissection revealed impending rupture because of false lumen infection 1 year after operation, and redo surgery was performed. Migration occurred in 3 patients, all with fusiform aneurysms. One of these had a graft kink 1 year later. Another showed aneurysm enlargement with serous pleural effusion 3 years after operation. The third required redo surgery because of perigraft leakage at 3 years after surgery. There were 2 late deaths caused by stroke. There were no EVG-related complications in the 9 cases in which anchoring sutures were applied and in the 7 cases with saccular aneurysms. No spinal cord dysfunction occurred in 8 cases with low-flow antegrade perfusion by way of both axillary arteries while the aorta was opened. Logistic regression analysis showed significant relevance to complications of large aneurysms, greater than 80 mm in diameter. A large aneurysm tends to give rise to complications involving EVG migration. Anchoring sutures of EVG may prevent EVG-related complications.

Aged↗

Novel pulse duplicating bioreactor system for tissue-engineered vascular construct.

Cell culture in a biomimetic environment is known to improve the mechanical endurance of tissue-engineered cardiovascular components. Our goal was to generate a bioreactor that can reproduce a wide range of pulsatile flows with a completely physiological pressure profile. The morphology and biochemical properties of tissue-engineered products were also studied to test the usefulness of this novel bioreactor. The combination of an outflow valve, compliance chamber, and resistant clamps together with a balloon pumping system was able to successfully reproduce both physiological systolic and diastolic pressures. The compliance chamber was especially effective in transforming the original peaky pressure waveform into a physiological pressure profile. The tissues, cultured under a physiological pressure waveform with pulsatile flow, presented widely distributed cells in close contact with each other. They also showed significantly higher cell numbers, total protein content, and proteoglycan-glycosaminoglycan content than cultured tissues under a peaky pressure wave or under static conditions. This new bioreactor system is suitable for evaluating a favorable environment for tissue-engineered cardiovascular components.

Animals↗

Evaluation of compliance and stiffness of decellularized tissues as scaffolds for tissue-engineered small caliber vascular grafts using intravascular ultrasound.

This study evaluated the compliance and stiffness of decellularized canine common carotid artery as well as decellularized canine ureter and compared it with that of polytetrafluoroethylene, elastin gel combined with polylactic acid tube, and canine common carotid artery. To calculate the compliance and stiffness, internal diameters and cross-sectional areas were measured according to changes in the intraluminal pressures using intravascular ultrasound in a closed circuit system equipped with a syringe pump. The pressure-area curve, stiffness parameter beta, and diameter compliance were evaluated. Canine common carotid artery and decellularized canine common carotid artery, as well as decellularized canine ureter, showed a compliant response, a J-shaped curve. However, the latter evidenced different characteristics in the low pressure range. Although the cross-sectional area of the elastin gel combined with polylactic acid tube showed some changes, it did not present a J-shape curve. Polytetrafluoroethylene exhibited a noncompliant response.The results in this study have shown that the compliance in the decellularized matrices was maintained after cell extraction, which demonstrated the importance of the remaining matrix structure in the mechanical properties of decellularized tissue. A clear difference between the decellularized matrices and synthetic materials was noted in terms of the compliance, even in materials composed of relatively elastic materials.

Animals↗